(AGENPARL) – ESCH-SUR-ALZETTE mar 06 giugno 2023
In a scientific article published in Nature metabolism, researchers from the University of Luxembourg show that a molecule secreted by a specific bacterium induces tumour growth and contributes to the progression of the disease. The study integrates in vitro, in vivo and in silico approaches. It highlights how animal research, combined with sophisticated methods, such as organoids and gut-on-chip models, helps gain a mechanistic understanding of cancer pathogenesis.
Prof. Elisabeth Letellier, head of the Molecular Disease Mechanisms team at the Department of Life Science and Medicine (DLSM) of the University of Luxembourg and project supervisor of the article, explains: “We rely on several approaches in a study like this one. Over time, scientists have developed cutting-edge techniques to mimic biological systems in the lab but none of them can fully reproduce the complexity of a living organism. We need mouse models to account for all of the existing parameters, especially in oncology where the interactions between different cell types are key and the whole microenvironment drives the disease.”
In this study, samples given by patients allowed the researchers to determine which microorganisms are associated with colorectal cancer and to identify a bacterium of interest: Fusobacterium nucleatum. Then, microfluidics devices, in which human cancer cells and bacteria are cultivated together, helped determine the effects of F. nucleatum and of a molecule it produces – formate. After studying the disease mechanisms in detail in the lab, the team was able to validate their findings thanks to animal models. Experiments in mice confirmed that the presence of the bacterium in the gut leads to increased tumour burden through the production of formate.
Formate, produced by F. nucleatum, promotes cancer stemness and metastatic dissemination of tumour cells.
These results constitute a step forward in understanding the complex interactions between the gut microbiome, the molecules it secretes and cancer metabolism, which will help to develop microbiome-based therapies in the future. They also underline that mouse models remain the gold standard in cancer research. “I think it is important to underline that we still need animal research: we are not there yet with the alternatives and it will be a long time before we can fully replace animal models,” details Prof. Letellier. “We need to be open about this and to ensure that we are doing everything the right way.”
Animal research has improved a lot over time. In the twenty years that she has been working with mice, Elisabeth Letellier has seen major improvements in terms of animal welfare and ethics. For example, the University of Luxembourg follows the 3R principles. Researchers look for alternatives when possible, refine protocols to minimise pain and reduce the number of animals by using statistical methods and advanced equipment. Among the recent and upcoming improvements, the installation of cages with an automated monitoring system and the purchase of an in vivo multiphoton laser-scanning microscope. The latter will allow scientists to observe the evolution of a disease over time in the same mouse, decreasing the number of animals needed. In addition to these technical transformations, the animal research mindset has evolved as well. “Everybody now understands that we have to strike a balance between our research objectives and animal welfare,” concludes Prof. Letellier. “And that to achieve it, researchers, vets, caretakers and members of the ethics committee have to work hand-in-hand. This is how we will keep pushing the boundaries of biomedical research.”
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Reference: Ternes D., Tsenkova M., Pozdeev V.I. et al., The gut microbial metabolite formate exacerbates colorectal cancer progression, Nature Metabolism, 4, 458–475 (2022). https://doi.org/10.1038/s42255-022-00558-0
Illustration created with BioRender.com
Fonte/Source: http://wwwfr.uni.lu/index.php/fstm/actualites/from_microfluidics_to_mouse_models_to_study_microbiome_in_cancer